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"Li, Min"
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Mechanisms of FOXK1-regulated glycolipid metabolism in mediating TOX-induced histone lactylation to promote CD8⁺ T cell exhaustion in high-grade serous ovarian cancer
To determine whether FOXK1 induces CD8⁺ T cell exhaustion via histone lactylation in high-grade serous ovarian cancer (HGSOC). Cellular studies utilized qRT-PCR and Western blotting to compare FOXK1 expression in normal ovarian vs. cancer cells. Western blot assessed proteins linked to aerobic glycolysis, lipid metabolism, histone ubiquitination, and epithelial-mesenchymal transition (EMT). Cell migration/invasion were evaluated via scratch and Transwell assays. In vivo, a mouse ovarian cancer model was established. Lactate and lipid levels in supernatants/tissues were measured using Oil Red O and detection kits. TOX and glucose and lipid metabolism regulatory factors were analyzed by H&E staining and immunohistochemistry. The expression levels of immune related factors and the proportion of positive immune detection points in the supernatant of CD8+ T cell culture and tumor tissue were detected by ELISA kits and flow cytometry. Ovarian cancer cells showed elevated FOXK1, glycolysis proteins, lipid regulators, histone ubiquitination, EMT markers, lactate, and lipids compared to normal cells. Tumor tissues exhibited higher glycolysis proteins, lipid regulators, ubiquitination, and lipids than non-cancerous tissue. FOXK1 knockdown in SKOV3 cells reduced lactate, lipids, glucose uptake, glycolysis/lipid proteins, and inhibited proliferation/migration/invasion, while enhancing CD8 + T cell proliferation, immune checkpoint positivity, and immune factors, with decreased apoptosis. In mice, FOXK1 knockdown reduced tumor volume, TOX, glycolipid regulators, ubiquitination, and lipids, but increased immune factors and checkpoint-positive cells in tissues. FOXK1 regulates glycolipid metabolism and TOX histone lactylation, driving CD8 + T cell exhaustion, suggesting novel immunotherapy targets.
Journal Article
Tales from dayrut
\"This collection of fourteen connected stories and a novella takes us deep into Upper Egypt and the village of Dayrut al-Sharif, in which Mohamed Mustagab was born. To depict a world renowned for its poverty, ignorance, vendettas, and implacable code of honor, Mustagab deploys the black humor and Swiftian sarcasm of the insider who knows his society only too well. When the stillness of a day's end is shattered by a single gunshot, poignant beauty merges seamlessly into horror, and when a police officer seeking to unravel a murder finds himself with more body parts than he knows what to do with, violence tips as easily into farce. In counterpoint, the author's often surrealist imagination explores the mysteries of a landscape where seductive women haunt dusty paths and a man may find himself crushed like a worm beneath another's foot. Elsewhere, the horizons of 'my village' expand to include other countries (the author worked in the Arabian Peninsula for a number of years), where equally disastrous consequences follow on folly and self-delusion. Previously almost unknown in English, Mustagab's voice is both original and disturbing.\"--Back cover.
Book
A novel nomogram to predict mortality in patients with stroke: a survival analysis based on the MIMIC-III clinical database
Background
Stroke is a disease characterized by sudden cerebral ischemia and is the second leading cause of death worldwide. We aimed to develop and validate a nomogram model to predict mortality in intensive care unit patients with stroke.
Methods
All data involved in this study were extracted from the Medical Information Mart for Intensive Care III database (MIMIC-III). The data were analyzed using multivariate Cox regression, and the performance of the novel nomogram, which assessed the patient’s overall survival at 30, 180, and 360 days after stroke, was evaluated using Harrell’s concordance index (C-index) and the area under the receiver operating characteristic curve. A calibration curve and decision curve were introduced to test the clinical value and effectiveness of our prediction model.
Results
A total of 767 patients with stroke were randomly divided into derivation (n = 536) and validation (n = 231) cohorts at a 7:3 ratio. Multivariate Cox regression showed that 12 independent predictors, including age, weight, ventilation, cardiac arrhythmia, metastatic cancer, explicit sepsis, Oxford Acute Severity of Illness Score or OASIS score, diastolic blood pressure, bicarbonate, chloride, red blood cell and white blood cell counts, played a significant role in the survival of individuals with stroke. The nomogram model was validated based on the C-indices, calibration plots, and decision curve analysis results.
Conclusions
The plotted nomogram accurately predicted stroke outcomes and, thus may contribute to clinical decision-making and treatment as well as consultation services for patients.
Journal Article
Guide to Metabolomics Analysis: A Bioinformatics Workflow
Metabolomics is an emerging field that quantifies numerous metabolites systematically. The key purpose of metabolomics is to identify the metabolites corresponding to each biological phenotype, and then provide an analysis of the mechanisms involved. Although metabolomics is important to understand the involved biological phenomena, the approach’s ability to obtain an exhaustive description of the processes is limited. Thus, an analysis-integrated metabolomics, transcriptomics, proteomics, and other omics approach is recommended. Such integration of different omics data requires specialized statistical and bioinformatics software. This review focuses on the steps involved in metabolomics research and summarizes several main tools for metabolomics analyses. We also outline the most abnormal metabolic pathways in several cancers and diseases, and discuss the importance of multi-omics integration algorithms. Overall, our goal is to summarize the current metabolomics analysis workflow and its main analysis software to provide useful insights for researchers to establish a preferable pipeline of metabolomics or multi-omics analysis.
Journal Article
Tuning defects in oxides at room temperature by lithium reduction
Defects can greatly influence the properties of oxide materials; however, facile defect engineering of oxides at room temperature remains challenging. The generation of defects in oxides is difficult to control by conventional chemical reduction methods that usually require high temperatures and are time consuming. Here, we develop a facile room-temperature lithium reduction strategy to implant defects into a series of oxide nanoparticles including titanium dioxide (TiO
2
), zinc oxide (ZnO), tin dioxide (SnO
2
), and cerium dioxide (CeO
2
). Our lithium reduction strategy shows advantages including all-room-temperature processing, controllability, time efficiency, versatility and scalability. As a potential application, the photocatalytic hydrogen evolution performance of defective TiO
2
is examined. The hydrogen evolution rate increases up to 41.8 mmol g
−1
h
−1
under one solar light irradiation, which is ~3 times higher than that of the pristine nanoparticles. The strategy of tuning defect oxides used in this work may be beneficial for many other related applications.
Defective oxides are attractive for energy conversion and storage applications, but it remains challenging to implant defects in oxides under mild conditions. Here, the authors develop a versatile lithium reduction strategy to engineer the defects of oxides at room temperature leading to enhanced photocatalytic properties.
Journal Article
Ankylosing spondylitis and psychiatric disorders in European population: a Mendelian randomization study
BackgroundEpidemiologic evidence has demonstrated a correlation between ankylosing spondylitis and psychiatric disorders. However, little is known about the common genetics and causality of this association. This study aimed to investigate the common genetics and causality between ankylosing spondylitis (AS) and psychiatric disorders.MethodsA two-sample Mendelian Randomization (MR) analysis was carried out to confirm causal relationships between ankylosing spondylitis and five mental health conditions including major depressive disorder (MDD), anxiety disorder (AXD), schizophrenia (SCZ), bipolar disorder (BIP), and anorexia nervosa (AN). Genetic instrumental variables associated with exposures and outcomes were derived from the largest available summary statistics of genome-wide association studies (GWAS). Bidirectional causal estimation of MR was primarily obtained using the inverse variance weighting (IVW) method. Other MR methods include MR-Egger regression, Weighted Median Estimator (WME), Weighted Mode, Simple Mode, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO). Sensitivity analyses are conducted to estimate the robustness of MR results.ResultsThe findings suggest that AS may be causally responsible for the risk of developing SCZ (OR = 1.18, 95% confidence interval = (1.06, 1.31), P = 2.58 × 10-3) and AN (OR = 1.32, 95% confidence interval = (1.07, 1.64), P = 9.43 × 10-3). In addition, MDD, AXD, SCZ, AN, and BIP were not inversely causally related to AS (all p > 0.05).ConclusionOur study provides fresh insights into the relationship between AS and psychiatric disorders (SCZ and AN). Furthermore, it may provide new clues for risk management and preventive interventions for mental disorders in patients with AS.
Journal Article
Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing
CRISPR-Cas9 has emerged as a powerful technology that relies on Cas9/sgRNA ribonucleoprotein complexes (RNPs) to target and edit DNA. However, many therapeutic targets cannot currently be accessed due to the lack of carriers that can deliver RNPs systemically. Here, we report a generalizable methodology that allows engineering of modified lipid nanoparticles to efficiently deliver RNPs into cells and edit tissues including muscle, brain, liver, and lungs. Intravenous injection facilitated tissue-specific, multiplexed editing of six genes in mouse lungs. High carrier potency was leveraged to create organ-specific cancer models in livers and lungs of mice though facile knockout of multiple genes. The developed carriers were also able to deliver RNPs to restore dystrophin expression in DMD mice and significantly decrease serum PCSK9 level in C57BL/6 mice. Application of this generalizable strategy will facilitate broad nanoparticle development for a variety of disease targets amenable to protein delivery and precise gene correction approaches.
Therapeutic targets of CRISPR-Cas can often not be accessed due to lack of carriers to deliver RNPs systematically. Here, the authors engineer modified lipid nanoparticles for delivery of gene editing proteins to specific tissues.
Journal Article
Atomic layer deposited Pt-Ru dual-metal dimers and identifying their active sites for hydrogen evolution reaction
Single atom catalysts exhibit particularly high catalytic activities in contrast to regular nanomaterial-based catalysts. Until recently, research has been mostly focused on single atom catalysts, and it remains a great challenge to synthesize bimetallic dimer structures. Herein, we successfully prepare high-quality one-to-one A-B bimetallic dimer structures (Pt-Ru dimers) through an atomic layer deposition (ALD) process. The Pt-Ru dimers show much higher hydrogen evolution activity (more than 50 times) and excellent stability compared to commercial Pt/C catalysts. X-ray absorption spectroscopy indicates that the Pt-Ru dimers structure model contains one Pt-Ru bonding configuration. First principle calculations reveal that the Pt-Ru dimer generates a synergy effect by modulating the electronic structure, which results in the enhanced hydrogen evolution activity. This work paves the way for the rational design of bimetallic dimers with good activity and stability, which have a great potential to be applied in various catalytic reactions.
Atomically precise control over elemental distributions presents a challenge in the preparation of catalytic nanomaterials. Here the authors report Pt-Ru bimetallic dimer structures through atomic layer deposition process and identify the roles of Pt and Ru in hydrogen evolution reaction.
Journal Article